Rituxan May Be New Tx Option in EGPA

High rates of improvement and reduced need for prednisolone in eosinophilic granulomatosis with polyangiitis.

Rituximab (Rituxan) seemed to be a viable treatment option in patients with eosinophilic granulomatosis with polyangiitis (EGPA), according to new research.

Treatment with repeat or single-course rituximab in 41 patients was associated with improvement in 83% by 6 months and 88% by 12 months. Remission was achieved by 34% at 6 months and 49% at 12 months, while partial response was experienced by 49% and 39%, respectively, reported Aladdin Mohammad, MD, from the Vasculitis and Lupus Clinic at Addenbrooke's Hospital in Cambridge, England, and colleagues.

Their study, the largest to date to evaluate rituximab treatment in EGPA, showed both a high efficacy rate and acceptable adverse event profile over 1 year of treatment, they wrote in the Annals of the Rheumatic Diseases.

The results place rituximab favorably against currently recommended glucocorticoid and cyclophosphamide therapies for EGPA (formerly known as Churg-Strauss syndrome), resulting in "high rates of improvement and reduced requirement of prednisolone," they noted.

They recommended consideration of rituximab treatment "both for refractory and relapsing diseases, especially for antineutrophil cytoplasmic antibody (ANCA)-positive patients, and also for newly diagnosed patients in whom traditional cytotoxic drugs are contraindicated or undesirable."

However, they also noted that "despite the good response rate in this study, complete withdrawal of glucocorticoids was generally not feasible, highlighting the unmet need for glucocorticoid-sparing agents in EGPA. Long-term outcome of the use of rituximab in EGPA and its role as maintenance treatment need to be addressed in future studies."

The study included 41 EGPA patients (21 women) treated with rituximab between 2003 and 2013 at four centers in Europe and the U.S.

Half of the patients (51%) had relapsing disease and 37% had refractory, with the remaining 12% receiving rituximab as first-line therapy for new onset disease.

Initial infusion was 375 mg/m2/week for 4 weeks, or two doses of 1,000 mg given 2 weeks apart. One patient received two doses of 800 mg at a 2-week interval.

Retreatment was given at 6 months for 22 patients and of these, 17 had another retreatment at 12 months.

Most patients were also pre-medicated with intravenous hydrocortisone 100 mg, and antihistamines (chlorpheniramine 10 mg or diphenhydramine 50 mg), as well as oral acetaminophen 1 g before each rituximab infusion.

The main outcome of the study was remission, defined as a Birmingham Vasculitis Activity Score (BVAS) of 0; partial response was defined as a 50% or greater reduction in BVAS compared with baseline.

The median BVAS decreased from 11 at baseline to 2 at 6 months (P<0.001) and 1 at 12 months (P<0.001 versus baseline and P=0.017 versus 6 months), the authors reported.

Most (80%) of ANCA-positive patients achieved remission at 12 months, while only 38% of ANCA-negative patients had this degree of response (P=0.013).

However, "the absence of ANCA should not be a barrier to use of rituximab to treat EGPA," they emphasized.

There was a steady decrease in prednisolone/prednisone intake over the course of the study period, from a median dose of 15 mg/day at baseline to 8 mg/day at 6 months and 12 months (P=0.001), reported the authors.

However, "only 6% of patients were off all treatment with prednisolone by the end of the observation period, indicating that rituximab in this cohort was not a fully glucocorticoid-sparing agent," they cautioned.

The study found no difference in the rate of response, type of response, or number of adverse events between patients with relapsing or refractory disease or those with different types of rituximab dosing.

Half of patients (51%) reported 31 adverse events.

While the frequency of severe adverse events was comparable with other experiences with rituximab in ANCA-associated vasculitis, "we observed a relatively high rate of infusion reactions, although most were mild," the authors wrote. "Our findings support the use of pre-medication with intravenous glucocorticoids and antihistamines to minimize allergic reactions in patients with EGPA."

The most common adverse events were infections in 15 patients, six of which were severe, and included chest infections, upper respiratory tract infections, and pyelonephritis. Ten infusion reactions occurred, eight of which were mild and resolved after temporarily stopping rituximab and adding glucocorticoids. Two severe reactions required admission to hospital and treatment with intravenous glucocorticoids (one with intubation for worsening asthma), they reported.

The retrospective study had some limitations, including different treatment protocols at the centers, especially when using other immunosuppressive drugs in combination with rituximab, the authors explained.

The study was funded by the Cambridge Biomedical Research Centre and The Swedish Society of Medicine.

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